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二甲双胍改变肿瘤免疫微环境,改善合并 2 型糖尿病的乳腺癌患者结局

英文原题:Metformin Alters Tumor Immune Microenvironment, Improving the Outcomes of Breast Cancer Patients With Type 2 Diabetes Mellitus.

查看英文原题

Metformin Alters Tumor Immune Microenvironment, Improving the Outcomes of Breast Cancer Patients With Type 2 Diabetes Mellitus.

PubMed 2024/02/23(内容时间) J Breast Cancer Q2 · IF 3.6(JCR 2025)

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中文摘要

本研究探讨了二甲双胍对既往患有2型糖尿病(T2DM)的乳腺癌患者的临床效果。我们分析了177例接受乳腺癌手术的T2DM患者,并使用多重免疫组化(IHC)评估了接受肿瘤切除且伴或不伴二甲双胍治疗患者的肿瘤相关巨噬细胞(TAMs)和TIL(肿瘤浸润淋巴细胞)(TILs)。与未接受二甲双胍治疗的患者相比,术前或术后接受二甲双胍治疗的患者远处器官复发减少,术后无复发生存改善。

此外,在40例接受术前全身治疗的亚组患者中,二甲双胍治疗与病理完全缓解率升高相关。IHC分析显示,与未接受二甲双胍治疗组相比,二甲双胍治疗组中分化簇(CD)68(+) CD163(+) M2型TAMs水平显著降低(p < 0.01),但CD3(+)和CD8(+) TIL密度更高,且CD8(+)/CD3(+) TIL比值差异显著(p < 0.01)。尽管我们的样本量较小带来了限制,但我们的研究结果提示,二甲双胍可能具有调节免疫微环境的作用,这可能有助于改善糖尿病合并乳腺癌患者的结局。

展开英文摘要原文

This study investigated the clinical effect of metformin on breast cancer patients with preexisting type 2 diabetes mellitus (T2DM).

We analyzed 177 patients with T2DM who underwent breast cancer surgery and assessed tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) in patients who underwent tumor resection with or without metformin treatment using multiplex immunohistochemistry (IHC). Patients who received metformin either pre- or postoperatively exhibited reduced distant organ recurrence and improved postoperative recurrence-free survival compared to those of patients who did not.

Additionally, in a subgroup of 40 patients receiving preoperative systemic therapy, metformin treatment was associated with increased rates of pathological complete response. IHC analysis revealed significantly lower levels of cluster of differentiation (CD) 68(+) CD163(+) M2-type TAMs ( p < 0.

01) but higher CD3(+) and CD8(+) TIL densities in the metformin-treated group compared with the same parameters in those without metformin treatment, with a significant difference in the CD8(+)/CD3(+) TIL ratio ( p < 0. 01). Despite the constraints posed by our small sample size, our findings suggest a potential role for metformin in modulating the immunological microenvironment, which may contribute to improved outcomes in diabetes patients with breast cancer.

论文信息

作者
Shiba S、Harao M、Saito A、Sakuragi M、Kitayama J、Sata N
第一作者单位
Department of Surgery, Jichi Medical University, Shimotsuke, Japan.Japan
通讯作者单位
Department of Breast Oncology, Jichi Medical University Hospital, Shimotsuke, Japan. kitayama@jichi.ac.jp.Japan
期刊
Journal of breast cancer2024 Apr
原文标识
PubMed 38529589 · DOI 10.4048/jbc.2023.0285